TY - JOUR
T1 - Pharmacokinetically and clinician-determined adherence to an antidepressant regimen and clinical outcome in the TORDIA Trial
AU - Woldu, Hiwot
AU - Porta, Giovanna
AU - Goldstein, Tina
AU - Sakolsky, Dara
AU - Perel, James
AU - Emslie, Graham
AU - Mayes, Taryn
AU - Clarke, Greg
AU - Ryan, Neal D.
AU - Birmaher, Boris
AU - Wagner, Karen Dineen
AU - Asarnow, Joan Rosenbaum
AU - Keller, Martin B.
AU - Brent, David
PY - 2011/5
Y1 - 2011/5
N2 - Objective: Nonadherence to antidepressant treatment may contribute to poor outcome and to suicidal adverse events in adolescent depression. We examine the relationship between adherence and both clinical response and suicidal events in participants in the Treatment of Resistant Depression in Adolescents (TORDIA) study. Method: The relationship between adherence to medication and clinical outcome was assessed in 190 treatment-resistant depressed adolescents who were randomized to one of four cells: switch to another selective serotonin reuptake inhibitor (SSRI), switch to venlafaxine, or either of these two medication switches plus cognitive behavioral therapy. Plasma levels of antidepressant drug and metabolites were determined after 6 and 12 weeks of treatment. A twofold or greater variation in the dose-adjusted concentration of drug plus metabolites (level/dose ratio [LDR]) was defined as nonadherence. Nonadherence was also determined by clinician pill counts (CPC) of the proportion of prescribed pills that were unused and was defined as having greater than 30% of the prescribed pills remaining. Results: LDR and CPC showed low concordance. LDR was unrelated to clinical response. CPC adherence was related to a higher response rate overall (adherent, 63.0% versus nonadherent, 47.2%, p = .03). Approximately half (50.8%) of the sample surveyed showed evidence of nonadherence by CPC. Neither measure of adherence was related to the occurrence of suicidal events or to the pace of decline in suicidal ideation. Conclusions: Clinician pill counts may be a relevant measure of adherence that is related to outcome under formal clinical trial conditions in depressed adolescents. Nonadherence appears to be a common and significant source of treatment nonresponse. Clinical Trial Registration InformationTreatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://www.clinicaltrials.gov; NCT00018902.
AB - Objective: Nonadherence to antidepressant treatment may contribute to poor outcome and to suicidal adverse events in adolescent depression. We examine the relationship between adherence and both clinical response and suicidal events in participants in the Treatment of Resistant Depression in Adolescents (TORDIA) study. Method: The relationship between adherence to medication and clinical outcome was assessed in 190 treatment-resistant depressed adolescents who were randomized to one of four cells: switch to another selective serotonin reuptake inhibitor (SSRI), switch to venlafaxine, or either of these two medication switches plus cognitive behavioral therapy. Plasma levels of antidepressant drug and metabolites were determined after 6 and 12 weeks of treatment. A twofold or greater variation in the dose-adjusted concentration of drug plus metabolites (level/dose ratio [LDR]) was defined as nonadherence. Nonadherence was also determined by clinician pill counts (CPC) of the proportion of prescribed pills that were unused and was defined as having greater than 30% of the prescribed pills remaining. Results: LDR and CPC showed low concordance. LDR was unrelated to clinical response. CPC adherence was related to a higher response rate overall (adherent, 63.0% versus nonadherent, 47.2%, p = .03). Approximately half (50.8%) of the sample surveyed showed evidence of nonadherence by CPC. Neither measure of adherence was related to the occurrence of suicidal events or to the pace of decline in suicidal ideation. Conclusions: Clinician pill counts may be a relevant measure of adherence that is related to outcome under formal clinical trial conditions in depressed adolescents. Nonadherence appears to be a common and significant source of treatment nonresponse. Clinical Trial Registration InformationTreatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://www.clinicaltrials.gov; NCT00018902.
KW - antidepressants
KW - depression
KW - medication adherence
UR - http://www.scopus.com/inward/record.url?scp=79955435624&partnerID=8YFLogxK
U2 - 10.1016/j.jaac.2011.01.018
DO - 10.1016/j.jaac.2011.01.018
M3 - Article
C2 - 21515198
AN - SCOPUS:79955435624
SN - 0890-8567
VL - 50
SP - 490
EP - 498
JO - Journal of the American Academy of Child and Adolescent Psychiatry
JF - Journal of the American Academy of Child and Adolescent Psychiatry
IS - 5
ER -